ABSTRACT At any one time, tens of thousands of children are living with serious illness and they and their families endure a high degree of suffering. While national recommendations call for early palliative care (PC) integration for seriously ill children to ease suffering, very few randomized controlled trials (RCTs) have evaluated whether PC improves child and family outcomes. In prior work, the investigators developed the Pediatric Quality of Life and Evaluation of Symptoms Technology (PediQUEST/PQ), a software that collects electronic Patient-Reported Outcomes (e-PROMS) and generates feedback reports. The effect of using PQ to provide feedback on child's symptoms and health related quality of life (HRQoL) to families and providers was tested in a three-site RCT, within the well established Pediatric PC Research Network, among 104 children ?2 years old with advanced cancer. The study demonstrated the feasibility of conducting a multisite RCT in this patient population, and an ability to obtain child self-report. Findings also included (a) high levels of child symptom distress, (b) association between higher symptom distress and worse HRQoL, (c) high parental psychological distress linked to child suffering, and (d) trends towards better HRQoL in the intervention arm. Subsequent formative research led to identification of barriers to improving symptom management including families and providers ?normalizing distress?, limited use of non-pharmacological treatment strategies, and limited early involvement of PC. Based on Wilson-Cleary's HRQoL model, and informed by these results, the PI and research team developed PQ Response (Response to Pediatric Oncology Symptom Experience). The intervention includes an enhanced PQ system (web-based), coupled with early integration of a PC consulting team (Response team). This dual strategy seeks to standardize the report of symptom distress using PQ feedback, and the providers' response to such distress, trained to include a series of steps in their assessment and interaction with the family including treatment and preventive strategies and family activation regarding symptom control. Pilot work for PQ Response found it feasible, well received by families and oncologists, and potentially effective. Thus, the over-riding aim of this study is to conduct a RCT of PQ Response versus usual care at four large pediatric oncology centers among children ?2 years old with advanced cancer (n=136). Hypotheses include a) children receiving the intervention will have better (higher) HRQoL scores b) parents of children in the intervention group will report better state-anxiety, depression and HRQoL and c) intervention group families will demonstrate higher levels of activation. Parents and children (if ?5 years old) in both arms will answer weekly PQ- Surveys for 16 weeks; parent anxiety, depression, and HRQoL will be assessed every 4-weeks; and parent activation every 8 weeks. Hypotheses will be tested using mixed effects models. The study will provide data on outcomes of early PC integration, use of e-PROMS and parent activation strategies in pediatrics, which are important knowledge gaps in palliative care research, and is well aligned with three key themes defined in NINR's strategic plan: science of symptoms, increased self-management, and palliative care.